IVF: effect of in-utero DES exposure on human egg quality and fertilization

Factors such as aneuploidy, embryonic genome expression and ultrastructure have not been assessed in this 1999 study.

Abstract

Effect of in-utero diethylstilboestrol exposure on human oocyte quality and fertilization in a programme of in-vitro fertilization, Human reproduction (Oxford, adiposity England), NCBI PubMed PMID 10357979, 1999 Jun.
Full study: Oxford Journals, Medicine & Health Human Reproduction Volume 14, Issue 6 Pp. 1578-1581 doi: 10.1093/humrep/14.6.1578, February 15, 1999.

Genital tract abnormalities and adverse pregnancy outcome are well known in women exposed in utero to diethylstilboestrol (DES).

Data about adverse reproductive performance in women exposed to DES have been published, including controversial reports of menstrual dysfunction, poor responses after ovarian stimulation, oocyte maturation and fertilization abnormalities.

We compared oocyte quality, in-vitro fertilization results and embryo quality for women exposed in utero to DES with a control group. Between 1989 and 1996, 56 DES-exposed women who had 125 in-vitro fertilization (IVF) attempts were retrospectively compared to a control group of 45 women with tubal disease, who underwent 73 IVF attempts. Couples suffering from male infertility were excluded. The parameters compared were oocyte quality (maturation abnormalities, immature oocyte, mature oocyte), fertilization and cleavage rate (per treated and metaphase II oocytes), and embryo quality (number and grade).

We found no significant difference in oocyte maturational status, fertilization rates, cleavage rates, embryo quality and development between DES-exposed subjects and control subjects. These results suggest that in-utero exposure to DES has no significant influence on oocyte quality and fertilization ability as judged during IVF attempts.

Discussion

In the group of in-utero DES-exposed women analysed here, the prevalence of ovulatory dysfunction and endometriosis was very high, but the number and quality of oocytes retrieved after stimulation were similar to those from women not exposed to DES.

The clinical pregnancy rate (number of cycles with fetal sacs on ultrasound) per embryo transfer was not significantly different between the two groups although lower in the IVF cycles performed in DES-exposed patients. Thus, lower delivery rate could be related to other important variables such as uterine defects and endometrial morphology and thickness as previously reported.

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Effects of Mullerian anomalies on in vitro fertilization outcome

image of IVF
Among women with Mullerian anomalies, those with DES exposure in utero demonstrated the poorest outcome.

Abstract

Effects of Mullerian anomalies on in vitro fertilization outcome, Journal of assisted reproduction and genetics, NCBI PubMed PMID: 11699126, 2001 Oct.
Full text: Journal of Assisted Reproduction and Genetics, Vol. 18, No. 10, 2001 PMC3455312, May 7, 2001.

PURPOSE
To assess the effect of Mullerian anomalies on pregnancy rates in women undergoing in vitro fertilization (IVF).

METHODS
The records of 37 patients with and 819 patients without Mullerian anomalies undergoing a first cycle of IVF between December 1995 and July 1998 were included in this retrospective study. Outcome variables included maximal estradiol level, number of days of stimulation, number of follicles, number of oocytes, fertilization rate, and ongoing/livebirth pregnancy rate.

RESULTS
Patients with Mullerian anomalies had a significantly lower ongoing pregnancy rate (8.3%) than did controls (24.8%). No patients with diethylstilbestrol (DES)-related anomalies had an ongoing pregnancy.

CONCLUSIONS
Among women with Mullerian anomalies, those with DES exposure in utero demonstrated the poorest outcome, with no ongoing pregnancies in 22 cycles. Physicians should use this information in counseling such patients about reproductive choices.

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Outcome of IVF in DES-exposed daughters: experience in the 90s

image of ivf-treatment-post
Infertile patients with a history of in utero exposure to DES exhibit a significantly impaired implantation rate following Iin vitro fertilization, and the outcome of assisted reproductive technology remains poor.

Abstract

Outcome of IVF in DES-exposed daughters: experience in the 90s, Journal of assisted reproduction and genetics, NCBI PubMed PMID: 9401869, 1997 Oct.
Full text: Journal of Assisted Reproduction and Genetics, Vol. 14, No. 9, 1997, NCBI PubMed PMC3454843, 1997 Oct.

Purpose
The outcome of in vitro fertilization (IVF) in a group of infertile women with a history of in utero exposure to diethylstilbestrol (DES) was analyzed. Records from an academic IVF program were retrospectively reviewed.

Methods
Seventeen infertile women with a self-reported history of exposure to DES in utero, attending the IVF unit at Massachusetts General Hospital (MGH) for assisted reproductive technology (ART), underwent 27 IVF cycles. Analysis of the outcome of IVF including implantation and ongoing pregnancy rates was performed. The data were compared with results from a group of 20 infertile patients with idiopathic infertility undergoing 27 IVF cycles at MGH during the same period. The patients in the two groups were matched for age, basal day 3 levels of follicle stimulating hormone and serum estradiol, and the number and quality of embryos transferred.

Results
The response to controlled ovarian hyperstimulation was comparable in the two groups. Significantly lower implantation and ongoing pregnancy rates following IVF and embryo transfer were seen in the utero DES-exposed group compared to the control patients.

  • This study confirms a poor outcome of IVF in infertile women with a history of in utero exposure to DES. The significantly impaired implantation rate (2%) following IVF in this category of infertile women is striking and concordant with earlier reported data.
  • The risk of ectopic pregnancy is quoted to be eight times greater in women with a history of exposure to DES and appears to be the leading factor contributing to a poor reproductive performance in this group.
  • No prognostic implication could be attributed to the presence of a T-shaped uterine cavity in terms of ability to conceive and carry a pregnancy to term. Of the two successful IVF cycles in the DES-exposed group, one of the patients had a T-shaped uterine abnormality, while in the second patient the uterine cavity was hypoplastic.

Conclusions
This study determined impaired implantation to be a major factor contributing to infertility in women undergoing IVF with a history of in utero exposure to DES. The ovarian response to controlled hyperstimulation, the fertilization and cleavage rates, and the embryo quality remain unaffected in these patients. The mechanism for implantation failure remains obscure and the prognosis for ART is guarded for patients exposed to DES in utero.

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Endometrial pattern in DES-exposed women undergoing IVF

undergoing-ivf
These 1996 study data suggested that endometrial pattern is one of the most significant variables for pregnancy outcome in DES-exposed women undergoing in-vitro fertilization.

Abstract

Endometrial pattern in diethylstilboestrol-exposed women undergoing in-vitro fertilization may be the most significant predictor of pregnancy outcome, Human reproduction (Oxford, England), NCBI PubMed PMID: 9021378, 1996 Dec. Full text: Human reproduction (1996) 11 (12): 2719-2723., oxfordjournals, 1996.

The objective of this study was to compare prospectively pregnancy outcome as it is related to ultrasonic endometrial echo pattern in women exposed to diethylstilboestrol (DES) in utero by their mother’s consumption with women not exposed to DES, all of whom were undergoing in-vitro fertilization (IVF).

Pregnancy outcome relative to endometrial thickness and pattern was evaluated in 540 cycles of IVF including DES (n = 50) and non-DES-exposed (n = 490) women. Endometrial patterns were designated as p1 = solid; p2 = ring; and p3 = intermediate.

  • DES patients exhibited p1 more often than the majority of the non-DES-exposed group.
  • There was no significant difference in endometrial thickness among the cycles where p1 was noted when comparing the DES (10.3 mm) with the non-DES-exposed (10.7 mm) groups.
  • Notably, within the group exhibiting p1, no pregnancies occurred in the 18 cycles of DES-exposed women compared with a 39.2% clinical pregnancy and 36.5% delivery rate in the non-DES-exposed controls (P < 0.0001 and P = 0.008 respectively).
  • Pregnancy rates were not significantly different in the cycles where the other endometrial patterns were found when comparing the two groups.

The impact of uterine shape on pregnancy outcome was also investigated.

  • A T-shaped uterine configuration was noted in 11 out of 18 (61.1%) cycles of DES-exposed women with pattern p1 compared with nine out of 23 (39.1%) with pattern p2.
  • Of cycles where a T-shaped uterus was demonstrated, none out of 11 (0%) with pattern p1 compared with four out of nine (44.4%) with pattern p2 resulted in pregnancy (P = 0.026).

These data suggest that endometrial pattern is one of the most significant variables for pregnancy outcome in DES-exposed women undergoing IVF.

It is our recommendation, based on the above results, that patients with a history of in-utero DES exposure who repeatedly demonstrate a solid endometrial pattern consider a gestational carrier as a possible means of achieving a biological offspring. Further investigation of both natural and hormone-replaced cycles in DES-exposed patients would address the potential for improvement of endometrial receptivity in these women. If improvement is possible, one could consider foregoing embryo replacement during the stimulated cycle with cryopreservation of the embryos for transfer at a later date. Perhaps midcycle endometnal sampling of DES-exposed women undergoing assisted reproductive technologies would help to define the endometrial variation.

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Are implantation and pregnancy outcome impaired in DES-exposed women after IVF and embryo transfer?

image of embryo-transfer
This 1990 study concluded that implantation and pregnancy outcome are impaired in DES-exposed women after Iin vitro fertilization.

Abstract

Are implantation and pregnancy outcome impaired in diethylstilbestrol-exposed women after in vitro fertilization and embryo transfer? Fertility and sterility, NCBI PubMed PMID: 2379627, 1990 Aug.

Forty-six infertile women with a history of diethylstilbestrol (DES) exposure in utero underwent 149 stimulation attempts for in vitro fertilization (IVF). The mean (+/- SE) number of preovulatory oocytes harvested at retrieval and transferred was 3.9 +/- 3.3 (536/138) and 2.6 +/- 1.4 (328/124).

When compared with patients with tubal factor infertility and less than or equal to 4 pre-embryos transferred, the clinical pregnancy rate (15.3% versus 22%) was not statistically different. However, the term/ongoing pregnancy rate was significantly lower in the study group (8% versus 16%). Comparison of the IVF outcome with different uterine anomalies as detected by hysterosalpingogram (n = 29) showed a trend for a worse prognosis in women with constrictions and a combination of T-shape and constrictions.

It is concluded that implantation and pregnancy outcome are impaired in DES-exposed women after IVF.

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Pregnancy after gamete intrafallopian transfer in a DES Daughter with primary infertility

Gamete-Intrafallopian-Tube-transfer image
This GIFT reproductive technique, tested here in 1988, may prove to be an effective treatment for some of the DES-exposed women.

Abstract

Pregnancy after gamete intrafallopian transfer in a woman with primary infertility and in utero exposure to diethylstilbestrol. A case report, The Journal of reproductive medicine, NCBI PubMed PMID: 3290479, 1988 May.

In utero exposure to diethylstilbestrol (DES) has an adverse effect on reproductive performance and may be associated with infertility.

Gamete intrafallopian transfer (GIFT) is a new reproductive technique that has been advocated as an alternative to in vitro fertilization in women with at least one normally functioning fallopian tube. The process involves the translaparoscopic placement of oocytes and sperm into the fallopian tube. The technique has been successful in treating infertility due to endometriosis, male factors and immunologic factors as well as unexplained infertility.

We accomplished the first successful GIFT procedure in a woman with significant uterine effects from prenatal DES exposure. This technique may prove to be an effective treatment for infertile women with DES exposure who have no adequate explanation for their infertility.

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Experience with DES-exposed infertile women in a program of IVF

image of in-vitro-fertilization
There were four pregnancies in 17 patients after 21 cycles of embryo transfers, for a pregnancy rate of 23.5% per patient, or 19% per embryo transfer.

Abstract

Experience with diethylstilbestrol-exposed infertile women in a program of in vitro fertilization, Fertility and sterility, NCBI PubMed PMID: 6724012, 1984 Jul.

Twenty infertile women with a history of diethylstilbestrol exposure in utero were seen in Norfolk for the purpose of in vitro fertilization.

Seventeen patients had undergone 25 stimulated cycles with harvest of oocytes by laparoscopy. The serum estradiol response to stimulation in these patients and the number and quality of oocytes retrieved did not differ significantly from those of patients with infertility due to blocked fallopian tubes.

  • There were four pregnancies in 17 patients after 21 cycles of embryo transfers, for a pregnancy rate of 23.5% per patient, or 19% per embryo transfer.
    • Two of the pregnant patients have had a term delivery,
    • one has had a preclinical abortion,
    • and one has a single intrauterine gestation in progress.
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